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PubMed2001

Weight loss is not associated with hyperleptinemia in humans with pancreatic cancer.

Pathological weight loss is a feature of many diseases and contributes to mortality and morbidity. Although cytokines have been implicated in some models of pathological weight loss, little is known about cellular mechanisms responsible for cachexia in patients with cancer. Leptin is a fat cell product that acts centrally to reduce appetite and decrease metabolism. Leptin synthesis is stimulated by cytokines, and circulating levels of cytokines are elevated in some cancer patients. We hypothesized that cytokine-induced hyperleptinemia contributes to pathological weight loss in patients with pancreatic cancer. To evaluate this hypothesis, fasting serum leptin concentrations were measured in 64 patients undergoing surgery for pancreatic cancer. Preoperative interviews were used to assess body weight and appetite history. Thirty of 64 pancreatic cancer patients had cachexia (weight loss of >10% over the 6 months before surgery). Self-reported loss of appetite was associated with the presence of cachexia. Leptin concentrations, when corrected for body mass index, were lower than levels reported in healthy humans. Six patients had leptin levels more than 2 times those predicted by body mass index. There was no association between patients with increased leptin concentration and weight loss or anorexia. We conclude that a reduced appetite contributes to weight loss in patients with pancreatic cancer. High plasma leptin levels, however, do not appear to contribute to cachexia in these patients.

Aged↗
PubMedDate not supplied

Evaluation of body condition and weight loss in dogs presented to a veterinary oncology service.

Cancer cachexia is a well-recognized syndrome in human patients that is characterized by progressive involuntary weight loss. The prevalence of this syndrome in veterinary cancer patients is unknown. This study's objective was to investigate the occurrence of weight loss and cachexia, as characterized by body condition scoring, in dogs presented to a veterinary oncology service. Information collected on 100 dogs included signalment, diagnosis, weight at time of diagnosis, and, when available, weight from a time approximately 12 months before diagnosis. Body condition was assessed by using a 9-point system based on body silhouette and palpation of adipose tissue (4-5 = optimal, 1 = extreme cachexia, 9 = extreme obesity). Muscle wasting was scored based on palpation of skeletal muscle (3 = no wasting, 2 = mild, 1 = moderate, 0 = severe). Only 4% of the dogs exhibited cachexia as defined by a body condition score < or = 3, whereas 29% were classified as markedly overweight (> or = 7). Fifteen percent had evidence of clinically relevant muscle wasting (< or = 1). Body weight from a time before the diagnosis of cancer was available for 64 dogs. At the time of diagnosis, 31% had maintained or gained weight, 31% had lost up to 5%, 14% had lost between 5 and 10%, and 23% had lost >10% of body weight. Overall, the percentage of dogs with signs indicating a decline in nutritional status was less than what has been reported for human cancer patients. Future studies should investigate the extent to which weight loss occurs in canine patients on an appropriate plane of nutrition as well as to establish whether an association exists between poor nutritional status and outcome in canine cancer patients.

Adipose Tissue↗
PubMed2001

Nutritional strategy in the management of heart failure in adults.

The incidence of congestive heart failure (CHF) is increasing in Westernized countries, and patients with CHF experience poor quality of life (functional impairment, high hospitalization rate and high mortality). Malnutrition occurring during the course of CHF is referred to as cardiac cachexia and is associated with higher mortality independent of the severity of CHF. Cardiac cachexia involving a loss of more than 10% of lean body mass can clinically be defined as a bodyweight loss of 7.5% of previous dry bodyweight in a period longer than 6 months. The energy requirements of patients with CHF, whether cachectic or not, are not noticeably modified since the increase in resting energy expenditure is compensated by a decrease in physical activity energy expenditure. Malnutrition in CHF has been ascribed to neurohormonal alterations, i.e. anabolic/catabolic imbalance and increased cytokine release. Anorexia may occur, particularly during acute decompensation of CHF. Function is impaired in CHF, because of exertional dyspnea and changes in skeletal muscle. Decreased exercise endurance seems to be related to decreased mitochondrial oxidative capacities and atrophy of type 1 fibers, which are attributed to alteration in muscle perfusion and are partially reversible by training. Malnutrition could also impair muscle function, because of decreased muscle mass and strength associated with decreased glycolytic capacities and atrophy of type 2a and 2b fibres. With respect to the putative mechanisms of cardiac cachexia, anabolic therapy (hormones or nutrients) and anticytokine therapy have been proposed, but trials are scarce and often inconclusive. In surgical patients with CHF, perioperative (pre- and postoperative) nutritional support has been shown to be effective in reducing the mortality rate. Long term nutritional supplementation trials in patients with CHF and cachexia are thus required to establish recommendations for the nutritional management of patients with CHF.

Alcohol Drinking↗
PubMed2001

Loss of skeletal muscle in cancer: biochemical mechanisms.

Patients with cancer often undergo a specific loss of skeletal muscle mass, while the visceral protein reserves are preserved. This condition known as cachexia reduces the quality of life and eventually results in death through erosion of the respiratory muscles. Nutritional supplementation or appetite stimulants are unable to restore the loss of lean body mass, since protein catabolism is increased mainly as a result of the activation of the ATP-ubiquitin-dependent proteolytic pathway. Several mediators have been proposed. An enhanced protein degradation is seen in skeletal muscle of mice administered tumour necrosis factor (TNF), which appears to be mediated by oxidative stress. There is some evidence that this may be a direct effect and is associated with an increase in total cellular-ubiquitin-conjugated muscle proteins. Another cytokine, interleukin-6 (IL-6), may play a role in muscle wasting in certain animal tumours, possibly through both lysosomal (cathepsin) and non-lysosomal (proteasome) pathways. A tumour product, proteolysis-inducing factor (PIF) is produced by cachexia-inducing murine and human tumours and initiates muscle protein degradation directly through activation of the proteasome pathway. The action of PIF is blocked by eicosapentaenoic acid (EPA), which has been shown to attenuate the development of cachexia in pancreatic cancer patients. When combined with nutritional supplementation EPA leads to accumulation of lean body mass and prolongs survival. Further knowledge on the biochemical mechanisms of muscle protein catabolism will aid the development of effective therapy for cachexia.

Animals↗
PubMed1998

[Alteration and clinical significance of plasma levels of tumor necrosis factor in chronic heart failure].

The plasma levels of tumor necrosis factor (TNF) were measured by enzyme-linked immunoabsorbent assay in 109 patients who were grouped as "non-heart failure" (n = 36), "heart failure" (n = 36) and "cachexia" (n = 37). The results showed that there was no obvious difference in caloric intake among the three groups. Mean plasma levels of TNF were increased in patients with heart failure (0.51 +/- 0.2 ng.ml-1, P < 0.05) and even higher in patients with cachexia (6.19 +/- 2.76 ng.ml-1, P < 0.01) than in patients with non-heart failure (0.085 +/- 0.025 ng.ml-1). In the group with enhanced plasma levels of TNF (TNF > 100 pg.ml-1), the incidence of cachexia (61.0%) was obviously greater than that in the group with normal levels of TNF (17.6%). These findings indicate that plasma levels of TNF are elevated in patients with heart failure; high levels of TNF may play an important role in the pathogenesis of cardiac cachexia.

Adult↗
PubMed1994

Tumor growth delay by laser-generated shock waves.

The antiproliferative effect of laser-generated shock waves (L-SW) was investigated on a human renal cell carcinoma, RC-8, grown subcutaneously in the nu/nu mouse. The RC-8 is characterized by the syndrome of humoral hypercalcemia of malignancy (HHM) associated with profound cachexia, increase of serum Ca level, hypophosphatemia, and an enhancement of serum parathyroid-like peptides. In this model system, the effects on cachexia and tumor growth were studied after a series of pulses (3-200) generated by a Candela LFDL/3 equipped pulsed-dye laser with optical fiber guided through a hypodermic needle with a 45 degrees angle bended tip, stuck through the skin of the mouse, and positioned directly below the tumor. The antitumor effect, expressed as a delay of tumor growth, was found to be dependent on number of pulses applied, tumor size, and growth rate (alpha). Treatment of RC-8 with alpha = 0.21 was effective only after 200 pulses combined with a tumor volume smaller than 100 mm3. Under these conditions a growth delay of approximately 8 days was observed, paralleled by delay of animal weight loss (cachexia). Under conditions of a decreased growth rate of RC-8 (alpha = 0.13), the susceptibility toward L-SW was found to be increased, expressed by a suppression of tumor growth after 100 pulses. However, no L-SW-associated delay of cachexia was observed under these latter conditions.

Animals↗
PubMed2004

Exercise as a Time-conditioning Effector in Chronic Disease: a Complementary Treatment Strategy.

Exercise has been widely believed to be a preventive and therapeutic aid in the treatment of various pathophysiological conditions such as cardiovascular disease and cancer. A common problem associated with such pathologies is cachexia, characterized by progressive weight loss and depletion of lean and fat body mass, and is linked to poor prognosis. As this syndrome comprises changes in many physiological systems, it is tempting to assume that the modulation of the psychoneuroimmunoendocrine axis could attenuate or even prevent cachexia progression in cancer patients. Cancer cachexia is characterized by a disruption in the rhythmic secretion of melatonin, an important time-conditioning effector. This hormone, secreted by the pineal gland, transmits circadian and seasonal information to all organs and cells of the body, synchronizing the organism with the photoperiod. Considering that exercise modulates the immune response through at least two different mechanisms-metabolic and neuroendocrine-we propose that the adoption of a regular exercise program as a complementary strategy in the treatment of cancer patients, with the exercise bouts regularly performed at the same time of the day, will ameliorate cachexia symptoms and increase survival and quality of life.

Journal Article↗
PubMed1999

Wasting in cancer.

Progressive weight loss is a common feature of many types of cancer and is responsible not only for a poor quality of life and poor response to chemotherapy, but also a shorter survival time than is found in patients with comparable tumors without weight loss. Although anorexia is common, a decreased food intake alone is unable to account for the changes in body composition seen in cancer patients, and increasing nutrient intake is unable to reverse the wasting syndrome. Although energy expenditure is increased in some patients, cachexia can occur even with a normal energy expenditure. Various factors have been investigated as mediators of tissue wasting in cachexia. These include cytokines such as tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), interferon-gamma (IFN-gamma) and leukemia inhibitory factor (LIF), as well as tumor-derived factors such as lipid mobilizing factor (LMF) and protein mobilizing factor (PMF), which can directly mobilize fatty acids and amino acids from adipose tissue and skeletal muscle respectively. Induction of lipolysis by the cytokines is thought to result from an inhibition of lipoprotein lipase (LPL), although clinical studies provide no evidence for an inhibition of LPL in the adipose tissue of cancer patients. Instead there is an increased expression of hormone sensitive lipase, the enzyme activated by LMF. Protein degradation in cachexia is associated with an increased activity of the ATP-ubiquitin-proteasome pathway. The biological activity of both the LMF and PMF was shown to be attenuated by eicosapentaenoic acid (EPA). Clinical studies show that this polyunsaturated fatty acid is able to stabilize the rate of weight loss and adipose tissue and muscle mass in cachectic patients with unresectable pancreatic cancer. Knowledge of the mechanism of cancer cachexia should lead to the development of new therapeutic agents.

Anorexia↗
PubMed2003

Paraneoplastic signs and symptoms of renal cell carcinoma: implications for prognosis.

PURPOSE: Renal cell carcinoma (RCC) can present with a wide range of signs and symptoms. To our knowledge we report the first study to describe the frequency of paraneoplastic findings in a modern RCC series and assess the prognostic significance of each finding. MATERIALS AND METHODS: Using the kidney cancer database at our institution 1,046 patients undergoing nephrectomy for RCC between 1989 and 2001 were assessed. The prognostic significance of symptoms present at diagnosis and findings on preoperative laboratory evaluation were examined in a univariate analysis as well as on multivariate analysis controlling for TNM stage, Fuhrman grade and Eastern Cooperative Oncology Group performance status (ECOG-PS). RESULTS: Mean followup to date of death or last contact for all patients was 40.3 months. Median time to death was 19.3 months. Most paraneoplastic signs and symptoms correlated with poor survival, although on multivariate analysis hypoalbuminemia, weight loss, anorexia and malaise predicted shorter survival. The frequency of each of these findings was 19.9%, 22.9%, 10.6% and 19.1%, respectively. Cachexia, defined as the presence of at least 1 of these findings, was noted in 35.3% of patients. Cachexia did not predict a higher recurrence rate in patients with localized disease and only malaise correlated with a decreased likelihood of responding to immunotherapy. CONCLUSIONS: Cachexia, defined as hypoalbuminemia, weight loss, anorexia or malaise, predicts worse survival after controlling for well established indicators of prognosis (TNM stage, Fuhrman grade and ECOG-PS). Consideration should be given to expanding the ECOG-PS to include measures for cachexia when applied to patients with RCC.

Analysis of Variance↗
PubMed1998

Regulation of pathogenicity in hop stunt viroid-related group II citrus viroids.

Nucleotide sequences were determined for two hop stunt viroid-related Group II citrus viroids characterized as either a cachexia disease non-pathogenic variant (CVd-IIa) or a pathogenic variant (CVd-IIb). Sequence identity between the two variants of 95.6% indicated a conserved genome with the principal region of nucleotide difference clustered in the variable (V) domain. Full-length viroid RT-PCR cDNA products were cloned into plasmid SP72. Viroid cDNA clones as well as derived RNA transcripts were transmissible to citron (Citrus medica L.) and Luffa aegyptiaca Mill. To determine the locus of cachexia pathogenicity as well as symptom expression in Luffa, chimeric viroid cDNA clones were constructed from segments of either the left terminal, pathogenic and conserved (T1-P-C) domains or the conserved, variable and right terminal (C-V-T2) domains of CVd-IIa or CVd-IIb in reciprocal exchanges. Symptoms induced by the various chimeric constructs on the two bioassay hosts reflected the differential response observed with CVd-IIa and -IIb. Constructs with the C-V-T2 domains region from clone-IIa induced severe symptoms on Luffa typical of CVd-IIa, but were non-symptomatic on mandarin as a bioassay host for the cachexia disease. Constructs with the same region (C-V-T2) from the clone-IIb genome induced only mild symptoms on Luffa, but produced a severe reaction on mandarin, as observed for CVd-IIb. Specific site-directed mutations were introduced into the V domain of the CVd-IIa clone to construct viroid cDNA clones with either partial or complete conversions to the CVd-IIb sequence. With the introduction of six site-specific changes into the V domain of the clone-IIa genome, cachexia pathogenicity was acquired as well as a moderation of severe symptoms on Luffa.

Base Sequence↗
PubMedDate not supplied

Plasma cytokine levels in cardiac chambers of patients with mitral stenosis with congestive heart failure.

To ascertain whether elevated levels of circulating proinflammatory cytokines in patients with advanced heart failure are due to congestive heart failure or due to cachexia or infection complicating heart failure, we measured prospectively plasma concentrations of tumor necrosis factor-alpha (TNF-alpha), interleukin-1 beta (IL-1 beta), interleukin 2 (IL-2), and interleukin-6 (IL-6) in 12 patients with mitral stenosis with moderate congestive heart failure, but not with cachexia or infection. Blood samples were obtained from the peripheral vein and right and left atria of the patients during percutaneous mitral valvuloplasty. Levels of TNF-alpha, IL-1 beta, IL-2, and IL-6 in the plasma form the peripheral vein and right and left atria of these patients were not elevated compared with those from the peripheral vein of a control group of 10 normal subjects. On the other hand, plasma levels of TNF-alpha but not IL-1 beta, IL-2 or IL-6, were elevated in 4 of 9 patients with congestive heart failure complicated with cachexia and/or infection. Our results suggest that proinflammatory cytokine levels are not elevated in congestive heart failure uncomplicated with cachexia or infection.

Adult↗
PubMed2000

Follistatin is a modulator of gonadal tumor progression and the activin-induced wasting syndrome in inhibin-deficient mice.

Inhibins and activins are dimeric proteins belonging to the transforming growth factor-beta superfamily. Follistatin is an activin-binding protein that antagonizes the function of activin via binding to its beta-subunits. Previously, we demonstrated that mice deficient in inhibin develop ovarian and testicular sex cord-stromal tumors of granulosa and Sertoli cell origin, with 100% penetrance as early as 4 weeks of age. Overproduction of activins in the serum directly causes a cachexia-like wasting syndrome that results in lethality of these mice at an early stage after the onset of the tumors. In an independent set of studies, overexpression of mouse follistatin using the mouse metallothionein I promoter in transgenic mice led to gonadal defects and eventual infertility, primarily due to local effects of follistatin in these tissues. Activin has a positive growth effect on gonadal tumor cells in culture and directly causes the cancer cachexia-like syndrome in inhibin-deficient mice via interaction with activin receptor type IIA in livers and stomachs. We therefore hypothesized that an activin antagonist such as follistatin can act as a physiological modifier, either locally or via the serum, to block the activin-mediated cancer cachexia-like syndrome in inhibin-deficient mice and/or slow the progression of gonadal cancers in these mice. To test this hypothesis, we generated mice that are homozygous mutant for the inhibin alpha null allele (i.e. inham1/inham1) and carry the mouse metallothionein I follistatin (MT-FS) transgene. Our results show that gonadal tumors that are histologically similar in most, but not all, cases to the tumors in inhibin-deficient mice develop in these inham1/inham1, MT-FS+ mice. However, inham1/inham1, MT-FS+ mice exhibit a less severe wasting syndrome, lower serum activin levels, and a statistically significant prolonged survival in a number of cases compared with mice deficient in inhibin alone. Thus, follistatin can act as a modulator of tumor growth and the activin-induced cancer cachexia-like syndrome in inhibin-deficient mice.

Activins↗
PubMed2000

Clonal diversity in the expression and stability of the metastatic capability of Leishmania guyanensis in the golden hamster.

Metastatic disease is a major concern of dermal leishmaniasis caused by Leishmania of the Viannia subgenus. The golden hamster provides an experimental model of systemic dissemination and cutaneous metastasis of Leishmania Viannia. We have exploited this model to examine the expression of parasite virulence in cloned populations derived from a strain of L. guyanensis previously shown to be highly metastatic in the hamster. Metastatic capacity manifested as dissemination throughout the lymphoid organs; cachexia and secondary cutaneous lesions were found to differ among clones, yielding a spectrum of virulence. The metastatic phenotype of clonal populations was stable over 5 sequential passages in hamsters. In addition, the low or high propensity to disseminate and produce cutaneous metastatic lesions was reproduced. Capacity to disseminate from the inoculation site was conserved following subcloning of metastatic clones that had been passaged in culture for several generations; clinical manifestations, cachexia, and cutaneous metastatic lesions were variably expressed. Dissemination of parasites and cachexia were significantly related (P = 0.004). Overall, cachexia was an earlier manifestation of dissemination than cutaneous metastases (P < 0.001). The reproducible expression of virulence phenotypes by discrete populations of Leishmania in the golden hamster provides an experimental model for clinically relevant expression of virulence in human leishmaniasis.

Animals↗
PubMedDate not supplied

Evaluation: complementarity and contradictoriness of cancer theories. A genetic perspective.

In this Chapter we evaluate complementarity and contradictoriness regarding theories and data of carcinogenesis described in this issue. Most theories and data are compatible with a multimutation model of carcinogenesis. There are a few authors having severe criticism regarding this mainstream. From a view of philosophy of science such criticism is valuable and this type of papers deserves careful evaluation. Zajicek has the most serious criticism. He argues that cachexia, due to the absence of essential molecules, induces the tumor which tries to produce these missing essential molecules. So, in his view, cachexia causes cancer instead of cancer cachexia. The implication is that cachexia should be treated. Duesberg argues that cancer is due to an imbalance of chromosomes rather than to cancer specific mutations. A few points and implications seem important: (a) Duesberg does not really object to a multimutation model; (b) he wants to defend the view that cancer can also be due to chromosomal imbalance, and (c) cancer due to chromosomal imbalance cannot be inherited, in contrast to cancer based on a mutation.

Cell Transformation, Neoplastic↗
PubMed1990

[Palliative therapy in cancer 2. Nutrition control].

Deterioration in nutritional status occurs late in the progress of cancers at certain sites, but at all stages in patients with gastrointestinal cancer. Weight loss with decrease in body fat and muscle wastage, occurs to a varying degree. Superficially, the clinical condition resembles simple food deprivation. However, the derangements in metabolism are often and some patients show an elevated resting energy expenditure, disturbances of carbohydrate, fat and protein metabolism and generally, a failure to adapt to reduced food intake, which is characteristic of cachexia. Cancer cachexia then becomes characterized by signs of marked negative energy and protein balance, including hypoalbuminemia, weight loss, and anemia. On the other hand, toxohormone extracted from tumor tissues was considered as the main cause to produce cancer cachexia. However, it has become clearer that cytokines, e.g. cachectin/TNF, IL-1, LT and IFN gamma play an important role to produce cachexia. Patients who are malnourished have an incidence of postoperative complications double that seen in adequately nourished patients. The effectiveness of cancer-chemotherapy is also different in nutritional status of patients. Although in patients requiring hyperalimentation, enteral nutritional support may feasible and enteral feeding has a distinct metabolic advantage compared with parenteral feeding, there is a definite role for total parenteral nutrition in patients who have severe chronic radiation enteritis, side effect of chemotherapy, weight loss and malabsorption. Tentative weight gain and correction of hypoalbuminemia without improving patient survival may be expected by this intravenous hyperalimentation.

Humans↗
PubMed1981

Metabolic alterations in a noncachectic animal tumor system.

The increased energy expended by the host to synthesize substrate, which is utilized by the tumor, is a potential cause of cancer cachexia. In vivo glucose and alanine kinetics were examined by tracer methodology in a sarcoma-bearing rat model. The effects of 3-mercaptopicolinic acid, a potent inhibitor of gluconeogenesis, was also examined on this model. Both tumor-bearing (TB) and nontumor bearing (NTB) animals were gaining weight prior to study and the tumors were relatively small. The TB animals had significantly lower plasma glucose and higher blood lactic acid levels compared with NTB animals. After inhibition of gluconeogenesis, the plasma glucose decreased and the blood lactate increased significantly more in TB than NTB animals. The glucose turnover rate was significantly greater in TB compared with NTB animals, as was the rate of glucose recycling and the rate of gluconeogenesis (alanine leads to glucose), both energy demanding processes. These results suggest that the tumor-bearing animal, even prior to significant cachexia, has an excess demand for energy, the provision of which may be a significant factor in malignant cachexia.

Alanine↗
PubMed1985

Critical evaluation of the role of nutritional support with chemotherapy.

Although weight loss has an adverse impact on cancer patient survival, the ability of caloric provision via total parenteral nutrition (TPN) to favorably influence outcome in chemotherapy-treated populations is not established. In randomized trials, no significant improvement in either response or survival was associated with TPN addition to chemotherapeutic treatment of adult patients with lymphoma, sarcoma, colon cancer, adenocarcinoma and small cell carcinoma of the lung, or testicular carcinoma. In two instances, TPN addition was associated with decreased survival, again raising the concern that caloric support in the absence of effective antitumor therapy might stimulate cancer growth. In any event, the hypothesis that nutritional repletion of a malnourished cancer patient receiving chemotherapy will improve clinical outcome remains to be critically tested, as studies demonstrating sequential improvement in lean body mass have not been reported. Most recently, consideration of potential mechanisms underlying the development of cancer cachexia has led to new strategies for nutritional intervention. For example, hypogonadism or low testosterone levels have been described in male patient populations with advanced cancer and correlated with weight loss and adverse outcome, leading to trial of replacement therapy with nandrolone decanoate. Similarly, the frequent identification of abnormal glucose metabolism in the patients with cancer cachexia has stimulated clinical trials with agents such as hydrazine sulfate and insulin designed to reverse the metabolic abnormality. Whether such efforts designed to alter metabolic abnormalities associated with cancer cachexia will improve clinical outcome will be determined in ongoing clinical trials.

Adult↗
PubMed2004

Palliative nutritional intervention in addition to cyclooxygenase and erythropoietin treatment for patients with malignant disease: Effects on survival, metabolism, and function.

BACKGROUND: The role of nutrition in the palliative treatment of patients with malignancy-related cachexia is unclear. The goal of the current study was to determine whether specialized, nutrition-focused patient care could improve integrated whole-body metabolism and functional outcome in unselected weight-losing patients with malignant disease who were receiving systemic antiinflammatory (cyclooxygenase [COX]-inhibitory) treatment along with erythropoietin (EPO) support. METHODS: Three hundred nine patients with malignant disease who experienced progressive cachexia due to solid tumors (primarily gastrointestinal lesions) were randomized to receive a COX inhibitor (indomethacin, 50 mg twice daily) and EPO (15-40,000 units per week) along with specialized, nutrition-focused patient care (oral nutritional support and home total parenteral nutrition [TPN]) provided on a patient-by-patient basis to attenuate inflammation, prevent anemia, and improve nutritional status. Control patients received the same indomethacin and EPO doses that study patients received without the added nutritional support. All patients were treated and followed until death. Biochemical assays (blood, liver, kidney, and thyroid), nutritional state assessment (food intake and body composition), and exercise testing with simultaneous measurement of whole-body respiratory gas exchange before and during exercise were performed before the start of treatment and then at regular intervals during the treatment period (every 2-30 months after treatment initiation). Statistical analyses were performed on 'intention-to-treat' and 'as-treated' bases. RESULTS: Home TPN was provided to approximately 50% of the study patients without severe complications. Over the entire observation period, rhEPO prevented the development of anemia in both study patients and control patients. Intention-to-treat analysis revealed an improvement in energy balance for nutritionally supported patients (P < 0.03); no other significant differences in outcome between study patients and control patients were observed. As-treated analysis demonstrated that patients receiving nutrition experienced prolonged survival (P < 0.01), which was accompanied by improved energy balance (P < 0.001), increasing body fat (P < 0.05), and a greater maximum exercise capacity (P < 0.04). A trend toward increased metabolic efficiency at maximum exercise (P < 0.06) for study patients relative to control patients also was observed. CONCLUSIONS: The results of the current study strongly support that nutrition is a limiting factor influencing survival and that nutritional support protects integrated metabolism and metabolic function in patients with progressive cachexia secondary to malignant disease.

Aged↗